Hematopoetic Cancers

Hematopoesis

Leukemia

New diagnoses each year in the US: 40, 800 Adults 3,500 Children 21,840 died of leukemia in 2010

Leukemia Lifetime Risk: 1/77 Median age of diagnosis = 66 YOA Median age of death = 73 YOA 5 year survival = 54.1%

Symptoms Headaches Vomiting Confusion Loss of Muscle Control Seizures Swollen Lymph Nodes Fevers Pallor Weakness or Fatigue Frequent Infections Bleeding and Bruising Swollen or Uncomfortable Abdomen Joint Pain

Risk Factors Radiation Smoking Chemotherapy Down Syndrome HTLV-1 Infection Family History

Lymphoblastic / Lymphocytic Cancers

Acute Lymphoblastic Leukemia Lifetime Risk: 1/799 Median age of diagnosis = 13 YOA Median age of death = 49 YOA 5 year survival = 65.2%

ALL Detection No evidence that screening improves outcomes Generally detected with presented illness

ALL Factoids ~5000 new cases each year Primarily affects children- > 50% or cases occur before 20 years of age. Most common childhood cancer (23% of childhood cancers) Hispanic > White > Black Males > Females

ALL Treatment Chemotherapy 2-3 years (1% die initially and another 1-3% die during initial remission). [>95% experience complete remission w/i 4 weeks] Some Pts have CNS involvement (WBCs in CNS-3%); Systemic + Intrathecal Chemotherapy + Cranial radiation. Some Pts have testicular involvement (2% of males) Systemic Chemotherapy + Testicular radiation

ALL Survival 5 year survival = 89% for children <15 (Best outcomes 1-9 YOA) 5 year survival = 50% for children Worse outcomes for > 20 YOA and < 6 MOA

Chronic Lymphoblastic Leukemia Lifetime Risk: 1/210 Median age of diagnosis = 72 YOA Median age of death = 79 YOA 5 year survival = %

CLL Detection No evidence that screening improves outcomes Generally detected with presented illness or routine CBC

CLL Factoids ~14,990 new cases each year Primarily in middle-aged and elderly adults- increasing frequency in successive decades of life. Often slow progression Hyperproliferative cells have both B- and T- cell surface antigens (CDs 19/20 and CD 5) White > Black > Hispanic > Asian Males (~2x) > Females

CLL Treatment Dependent upon staging, no treatment (stage 0) to combination chemotherapy 2-3 years + / - radiation (stages I-IV) [Little evidence suggesting improved survival with these treatments] Symptomatic treatment Bone marrow transplant [Under clinical investigation, particularly for males < 60 YOA at diagnosis] Complications of non-treatment include ‘hyperviscosity syndrome’, autoimmune hemolytic anemia, and opportunistic infections resulting from hypogammaglobinemia

Hairy Cell Leukemia Abnormal B Cells 80% Affected = Adult Male Average age of diagnosis = 55 YOA

Myelogenous Cancers (Myelocytic / Myeloblastic)

Acute Myeloid Leukemia Lifetime Risk: 1/266 Median age of diagnosis = 67 YOA Median age of death = 72 YOA 5 year survival = 23.6%

AML Detection No evidence that screening improves outcomes Generally detected with presented illness or routine CBC

AML Factoids ~12,330 new cases each year primarily in middle-aged and elderly adults. All races approximate equal prevalence with White slightly higher Males > Females Some Pts have CNS involvement (5%)

AML Treatment Systemically administered combination chemotherapy treatment divided into two phases: remission induction (to attain remission) and post-remission (to maintain remission). Blood composition complications must be treated by replacement therapy and/or myeloid growth factor (e.g., GM-CSF) administration. Bone marrow transplant—30% cure rate in Pts who have experienced an early relapse following remission

AML Treatment Factoids Approximately 60% to 70% of adults with AML can be expected to attain complete remission following therapy. More than 25% of adults with AML (about 45% of those who attain complete remission) can be expected to survive 3 or more years and may be cured. Remission rates in adult AML are inversely related to age, and remissions are generally shorter in older patients. Other adverse prognostic factors include central nervous system involvement. systemic infection at diagnosis, elevated white blood cell count (>100,000/mm 3 ), treatment-induced AML, and others.

Chronic Myeloid Leukemia Lifetime Risk: 1/635 Median age of diagnosis = 65 YOA Median age of death = 74 YOA 5 year survival = 56.8% (median survival 4-6 years)

CML Detection Splenomegaly (although 10% of Pts have no splenic enlargement. Chronic ( 20%) [increasing immature myeloid cells] Anemia

CML Factoids ~4870 new cases each year >95% of patients have a distinctive cytogenetic abnormality, the “Philadelphia chromosome”. All races approximate equal prevalence with Hispanic and Asian slightly lower Males (~2x) > Females

CML Treatment Survival following ‘accelerated phase’ is generally < 1 year Pts with Ph1-negative CML generally have a poorer response to treatment and shorter survival than Ph1-positive pts. Imatinib (Y-kinase inhibitor) for Ph1-positive Pts. (2 years-indefinitely) Interferon-  Other chemotherapy Bone marrow transplant

Lymphoma

New diagnoses each year in the US: 71,810 Adults 2,220 Children 21,530 died of lymphoma in 2010

Lymphoma Median age of diagnosis = 64 YOA Median age of death = 75 YOA 5 year survival = 70.1%

Hodgkin Lymphoma Lifetime Risk: 1/428 Median age of diagnosis = 38 YOA Median age of death = 63 YOA 5 year survival = 84.7%

Detection Unexplained loss of more than 10% of body weight in the 6 months before diagnosis. Unexplained fever with temperatures above 38°C. Drenching night sweats. Confirmed by biopsy and/or CT scan 5% of Pts have bone marrow involvement

Hodgkin Lymphoma Factoids ~8490 new cases each year All races approximate equal prevalence with Asian 2x lower Males > Females

Stage Distribution and 5-year Relative Survival by Stage at Diagnosis Stage Distribution and 5-year Relative Survival by Stage at Diagnosis for , All Races, Both Sexes Stage at Diagnosis Stage Distribution (%) 5-year Relative Survival (%) Localized (confined to primary site) Regional (spread to regional lymphnodes) Distant (cancer has metastasized) Unknown (unstaged)582.3

Hodgkin Treatment Chemotherapy + Radiation Therapy to affected lymph nodes Pts who do not respond to chemotherapy (about 10%–20% of all presenting pts) have <10% survival rate at 8 years

Non-Hodgkin Lymphoma Lifetime Risk: 1/48 Median age of diagnosis = 67 YOA Median age of death = 75 YOA 5 year survival = 67.4%

NHL Detection Unexplained loss of more than 10% of body weight in the 6 months before diagnosis. Unexplained fever with temperatures above 38°C. Drenching night sweats. The majority of pts present with advanced (stage III or stage IV) disease that is often identified with CT scanning and biopsies of the bone marrow

NHL Factoids 65,540 new cases each year B Cell and T Cell Varieties: B Cell: 14-20/100,000; median age at diagnosis = 67 T Cell: 14-23/1,000,000; median age at diagnosis = 59 White > Black, Hispanic and Asian Males > Females Less predictable than Hodgkin lymphoma with a far greater predilection to disseminate to extranodal sites.

Non-Hodgkin Lymphoma Treatments Varies with staging, ranging from ‘watchful waiting, to chemotherapy + / - radiation Therapy to affected lymph nodes Rituximab (anti CD20) for B Cell variety